330 research outputs found

    A Monte Carlo global analysis of the Standard Model Effective Field Theory: the top quark sector

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    We present a novel framework for carrying out global analyses of the Standard Model Effective Field Theory (SMEFT) at dimension-six: SMEFiT. This approach is based on the Monte Carlo replica method for deriving a faithful estimate of the experimental and theoretical uncertainties and enables one to construct the probability distribution in the space of the SMEFT degrees of freedom. As a proof of concept of the SMEFiT methodology, we present a first study of the constraints on the SMEFT provided by top quark production measurements from the LHC. Our analysis includes more than 30 independent measurements from 10 different processes at 8 and 13 TeV such as inclusive top-quark pair and single-top production and the associated production of top quarks with weak vector bosons and the Higgs boson. State-of-the-art theoretical calculations are adopted both for the Standard Model and for the SMEFT contributions, where in the latter case NLO QCD corrections are included for the majority of processes. We derive bounds for the 34 degrees of freedom relevant for the interpretation of the LHC top quark data and compare these bounds with previously reported constraints. Our study illustrates the significant potential of LHC precision measurements to constrain physics beyond the Standard Model in a model-independent way, and paves the way towards a global analysis of the SMEFT.Comment: 76 pages, 24 figures, version accepted for publication in JHE

    The single-cell pathology landscape of breast cancer.

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    Single-cell analyses have revealed extensive heterogeneity between and within human tumours1-4, but complex single-cell phenotypes and their spatial context are not at present reflected in the histological stratification that is the foundation of many clinical decisions. Here we use imaging mass cytometry5 to simultaneously quantify 35 biomarkers, resulting in 720 high-dimensional pathology images of tumour tissue from 352 patients with breast cancer, with long-term survival data available for 281 patients. Spatially resolved, single-cell analysis identified the phenotypes of tumour and stromal single cells, their organization and their heterogeneity, and enabled the cellular architecture of breast cancer tissue to be characterized on the basis of cellular composition and tissue organization. Our analysis reveals multicellular features of the tumour microenvironment and novel subgroups of breast cancer that are associated with distinct clinical outcomes. Thus, spatially resolved, single-cell analysis can characterize intratumour phenotypic heterogeneity in a disease-relevant manner, with the potential to inform patient-specific diagnosis

    Direct Observation of Martensitic Phase-Transformation Dynamics in Iron by 4D Single-Pulse Electron Microscopy

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    The in situ martensitic phase transformation of iron, a complex solid-state transition involving collective atomic displacement and interface movement, is studied in real time by means of four-dimensional (4D) electron microscopy. The iron nanofilm specimen is heated at a maximum rate of ∼10^(11) K/s by a single heating pulse, and the evolution of the phase transformation from body-centered cubic to face-centered cubic crystal structure is followed by means of single-pulse, selected-area diffraction and real-space imaging. Two distinct components are revealed in the evolution of the crystal structure. The first, on the nanosecond time scale, is a direct martensitic transformation, which proceeds in regions heated into the temperature range of stability of the fcc phase, 1185−1667 K. The second, on the microsecond time scale, represents an indirect process for the hottest central zone of laser heating, where the temperature is initially above 1667 K and cooling is the rate-determining step. The mechanism of the direct transformation involves two steps, that of (barrier-crossing) nucleation on the reported nanosecond time scale, followed by a rapid grain growth typically in ∼100 ps for 10 nm crystallites

    Parton distributions from high-precision collider data: NNPDF Collaboration

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    We present a new set of parton distributions, NNPDF3.1, which updates NNPDF3.0, the first global set of PDFs determined using a methodology validated by a closure test. The update is motivated by recent progress in methodology and available data, and involves both. On the methodological side, we now parametrize and determine the charm PDF alongside the light-quark and gluon ones, thereby increasing from seven to eight the number of independent PDFs. On the data side, we now include the D0 electron and muon W asymmetries from the final Tevatron dataset, the complete LHCb measurements of W and Z production in the forward region at 7 and 8 TeV, and new ATLAS and CMS measurements of inclusive jet and electroweak boson production. We also include for the first time top-quark pair differential distributions and the transverse momentum of the Z bosons from ATLAS and CMS. We investigate the impact of parametrizing charm and provide evidence that the accuracy and stability of the PDFs are thereby improved. We study the impact of the new data by producing a variety of determinations based on reduced datasets. We find that both improvements have a significant impact on the PDFs, with some substantial reductions in uncertainties, but with the new PDFs generally in agreement with the previous set at the one-sigma level. The most significant changes are seen in the light-quark flavor separation, and in increased precision in the determination of the gluon. We explore the implications of NNPDF3.1 for LHC phenomenology at Run II, compare with recent LHC measurements at 13 TeV, provide updated predictions for Higgs production cross-sections and discuss the strangeness and charm content of the proton in light of our improved dataset and methodology. The NNPDF3.1 PDFs are delivered for the first time both as Hessian sets, and as optimized Monte Carlo sets with a compressed number of replicas.V. B., N. H., J. R., L. R. and E. S. are supported by an European Research Council Starting Grant “PDF4BSM”. R. D. B. and L. D. D. are supported by the UK STFC grants ST/L000458/1 and ST/P000630/1. L. D. D. is supported by the Royal Society, Wolfson Research Merit Award, grant WM140078. S. F. is supported by the European Research Council under the Grant Agreement 740006NNNPDFERC-2016-ADG/ERC-2016-ADG. E. R. N. is supported by the UK STFC grant ST/M003787/1. S. C. is supported by the HICCUP ERC Consolidator grant (614577). M. U. is supported by a Royal Society Dorothy Hodgkin Research Fellowship and partially supported by the STFC grant ST/L000385/1. S. F and Z. K. are supported by the Executive Research Agency (REA) of the European Commission under the Grant Agreement PITN-GA-2012-316704 (HiggsTools). A. G. is supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 659128-NEXTGENPDF

    Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis

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    Although macrophages are widely recognized to have a profibrotic role in inflammation, we have used a highly tractable CCl(4)-induced model of reversible hepatic fibrosis to identify and characterize the macrophage phenotype responsible for tissue remodeling: the hitherto elusive restorative macrophage. This CD11B(hi) F4/80(int) Ly-6C(lo) macrophage subset was most abundant in livers during maximal fibrosis resolution and represented the principle matrix metalloproteinase (MMP) -expressing subset. Depletion of this population in CD11B promoter–diphtheria toxin receptor (CD11B-DTR) transgenic mice caused a failure of scar remodeling. Adoptive transfer and in situ labeling experiments showed that these restorative macrophages derive from recruited Ly-6C(hi) monocytes, a common origin with profibrotic Ly-6C(hi) macrophages, indicative of a phenotypic switch in vivo conferring proresolution properties. Microarray profiling of the Ly-6C(lo) subset, compared with Ly-6C(hi) macrophages, showed a phenotype outside the M1/M2 classification, with increased expression of MMPs, growth factors, and phagocytosis-related genes, including Mmp9, Mmp12, insulin-like growth factor 1 (Igf1), and Glycoprotein (transmembrane) nmb (Gpnmb). Confocal microscopy confirmed the postphagocytic nature of restorative macrophages. Furthermore, the restorative macrophage phenotype was recapitulated in vitro by the phagocytosis of cellular debris with associated activation of the ERK signaling cascade. Critically, induced phagocytic behavior in vivo, through administration of liposomes, increased restorative macrophage number and accelerated fibrosis resolution, offering a therapeutic strategy to this orphan pathological process

    The Type III Effectors NleE and NleB from Enteropathogenic E. coli and OspZ from Shigella Block Nuclear Translocation of NF-κB p65

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    Many bacterial pathogens utilize a type III secretion system to deliver multiple effector proteins into host cells. Here we found that the type III effectors, NleE from enteropathogenic E. coli (EPEC) and OspZ from Shigella, blocked translocation of the p65 subunit of the transcription factor, NF-κB, to the host cell nucleus. NF-κB inhibition by NleE was associated with decreased IL-8 expression in EPEC-infected intestinal epithelial cells. Ectopically expressed NleE also blocked nuclear translocation of p65 and c-Rel, but not p50 or STAT1/2. NleE homologues from other attaching and effacing pathogens as well OspZ from Shigella flexneri 6 and Shigella boydii, also inhibited NF-κB activation and p65 nuclear import; however, a truncated form of OspZ from S. flexneri 2a that carries a 36 amino acid deletion at the C-terminus had no inhibitory activity. We determined that the C-termini of NleE and full length OspZ were functionally interchangeable and identified a six amino acid motif, IDSY(M/I)K, that was important for both NleE- and OspZ-mediated inhibition of NF-κB activity. We also established that NleB, encoded directly upstream from NleE, suppressed NF-κB activation. Whereas NleE inhibited both TNFα and IL-1β stimulated p65 nuclear translocation and IκB degradation, NleB inhibited the TNFα pathway only. Neither NleE nor NleB inhibited AP-1 activation, suggesting that the modulatory activity of the effectors was specific for NF-κB signaling. Overall our data show that EPEC and Shigella have evolved similar T3SS-dependent means to manipulate host inflammatory pathways by interfering with the activation of selected host transcriptional regulators

    Parton distribution benchmarking with LHC data

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    We present a detailed comparison of the most recent sets of NNLO PDFs from the ABM, CT, HERAPDF, MSTW and NNPDF collaborations. We compare parton distributions at low and high scales and parton luminosities relevant for LHC phenomenology. We study the PDF dependence of LHC benchmark inclusive cross sections and differential distributions for electroweak boson and jet production in the cases in which the experimental covariance matrix is available. We quantify the agreement between data and theory by computing the χ 2 for each data set with all the various PDFs. PDF comparisons are performed consistently for common values of the strong coupling. We also present a benchmark comparison of jet production at the LHC, comparing the results from various available codes and scale settings. Finally, we discuss the implications of the updated NNLO PDF sets for the combined PDF+α s uncertainty in the gluon fusion Higgs production cross section
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